Results of an initial study suggest that a single oral administration of retinoic acid (RA) was effective in enhancing the recovery rate of odor-mediated functions in adult mice after denervation. RA was used because it is a metabolite important in the development and growth of the olfactory system and may have potential in affecting olfactory recovery after denervation. The olfactory system provides an ideal model for studying neurogenesis because it has the ability to replace old and injured olfactory neurons throughout the life of the animal. An animal model for olfactory denervation has been established in which olfactory nerves are cut at the level of the cribriform plate, resulting in the degeneration of mature olfactory neurons and a complete loss of smell. With time, new olfactory neurons establish connections with the bulbs and olfactory functions are restored. The purpose of this application is to conduct initial experiments needed to understand the phenomenon of RA-aided recovery of olfactory functions. Behavioral and immunohistochemical methods will be used to: 1) determine the lowest effective dose of RA needed to enhance recovery of olfactory functions; 2) determine the most effective time for RA administration to enhance recovery of olfactory functions; and 3) identify the process affected by RA in the olfactory neurons. Results from this application will lead to future studies that will focus on the other factors that may influence the effectiveness of RA and the cellular mechanisms involved in RA-aided recovery of olfactory functions. In addition, the results will have important implications for understanding the regenerative properties of the olfactory system and may lead to treatments for human anosmia induced by head injury.